Mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) in carcinogenesis

Martin-Kleiner, Irena; Trošelj, Koraljka Gall

doi:10.1016/j.canlet.2009.06.036

Cited by 53 publications

(52 citation statements)

References 88 publications

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“…Colony-stimulating factor 1/CD115 (CSF1R) modulates a number of myeloid differentiation steps and inhibitors have been designed for a number of disease states (Hume and Macdonald, 2012). CD222/ insulin-like growth factor-2 (IGF2R) has long been recognized as a cancer-expressed protein (Martin-Kleiner and Gall Troselj, 2010). Each of these receptors should be explored as targets in ASPS.…”

Section: Resultsmentioning

confidence: 99%

Identification of Cell Surface Proteins as Potential Immunotherapy Targets in 12 Pediatric Cancers

Orentas¹,

Yang²,

Wen³

et al. 2012

Front. Oncol.

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Technological advances now allow us to rapidly produce CARs and other antibody-derived therapeutics targeting cell surface receptors. To maximize the potential of these new technologies, relevant extracellular targets must be identified. The Pediatric Oncology Branch of the NCI curates a freely accessible database of gene expression data for both pediatric cancers and normal tissues, through which we have defined discrete sets of over-expressed transcripts in 12 pediatric cancer subtypes as compared to normal tissues. We coupled gene expression profiles to current annotation databases (i.e., Affymetrix, Gene Ontology, Entrez Gene), in order to categorize transcripts by their sub-cellular location. In this manner we generated a list of potential immune targets expressed on the cell surface, ranked by their difference from normal tissue. Global differences from normal between each of the pediatric tumor types studied varied, indicating that some malignancies expressed transcript sets that were more highly diverged from normal tissues than others. The validity of our approach is seen by our findings for pre-B cell ALL, where targets currently in clinical trials were top-ranked hits (CD19, CD22). For some cancers, reagents already in development could potentially be applied to a new disease class, as exemplified by CD30 expression on sarcomas. Moreover, several potential new targets shared among several pediatric solid tumors are herein identified, such as MCAM (MUC18), metadherin (MTDH), and glypican-2 (GPC2). These targets have been identified at the mRNA level and are yet to be validated at the protein level. The safety of targeting these antigens has yet to be demonstrated and therefore the identified transcripts should be considered preliminary candidates for new CAR and therapeutic antibody targets. Prospective candidate targets will be evaluated by proteomic analysis including Westerns and immunohistochemistry of normal and tumor tissues.

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Section: Resultsmentioning

confidence: 99%

Identification of Cell Surface Proteins as Potential Immunotherapy Targets in 12 Pediatric Cancers

Orentas¹,

Yang²,

Wen³

et al. 2012

Front. Oncol.

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“…This receptor consists of 2491 amino acids counting from the first methionine encoded by ATG. It is a multiple ligand-binding cell surface receptor that is ubiquitously expressed in human tissues (Martin-Kleiner and Gall Troselj, 2010).…”

Section: Introductionmentioning

confidence: 99%

Biallelic transcription of the porcine IGF2R gene

Braunschweig

2012

Gene

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“…IGF2R has been recognized as a multifunctional receptor but not as a tyrosine kinase receptor [15, 16]. However, an in vitro study [17] revealed that IGF2R knockdown significantly reduced IGF2-related ERK1/2 phosphorylation, suggesting that the complex of IGF2 and IGF2R participates in cancer cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of IGF2 and IGF2 receptor in malignant solitary fibrous tumor with hypoglycemia: a case report

et al. 2018

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BackgroundSolitary fibrous tumor (SFT) is a prototypical mesenchymal neoplasm that induces non-islet cell tumor hypoglycemia (NICTH) due to overproduction of insulin-like growth factor 2 (IGF2). We here report the case of a malignant SFT associated with a hypoglycemia attack.Case presentationAn 81-year-old man with a large subphrenic mass presented with hypoglycemia and loss of consciousness. His serum insulin and IGF1 levels were relatively low, suggesting an excessively high serum IGF2 levels. Preoperative Western blotting of serum confirmed the overproduction of high-molecular-weight IGF2. After total tumor resection, the patient recovered from hypoglycemia without the need for further treatment. Histological examination revealed proliferation of spindle cells and frequent nuclear mitoses with STAT6 and CD34 immunoreactivity, which led to the diagnosis of malignant SFT. IGF2 was strongly upregulated in the tumor upon immunohistochemistry, consistent with the report of NICTH. In addition, the tumor expressed IGF2 receptor (IGF2R) but not IGF1R.ConclusionsThe present results indicate that the tumor co-expressed IGF2 and IGF2R. IGF2R has not previously been recognized as a tyrosine kinase receptor participating in cell signal transduction. Thus, further case series are required to determine whether IGF2R overexpression reflects the action of an unknown autocrine/paracrine system involving IGF2 for cell proliferation or for the scavenging and degradation of IGF2.

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Mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) in carcinogenesis

Cited by 53 publications

References 88 publications

Identification of Cell Surface Proteins as Potential Immunotherapy Targets in 12 Pediatric Cancers

Identification of Cell Surface Proteins as Potential Immunotherapy Targets in 12 Pediatric Cancers

Biallelic transcription of the porcine IGF2R gene

Overexpression of IGF2 and IGF2 receptor in malignant solitary fibrous tumor with hypoglycemia: a case report

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